Many techniques currently exist for delivering drugs or other medicaments to body tissue. Examples of current techniques include oral administration; injection directly into body tissue, such as through an intramuscular injection; topical or transcutaneous administration where the drug is passively absorbed, or caused to pass, into or across the skin or other surface tissue; and intravenous administration, which involves introducing a selected drug directly into the blood stream.
Except for topical or transcutaneous administration, the above drug delivery systems tend to be systemic. In other words, administration of the drug is delivered throughout the body by the blood stream.
Systemic administration of a drug is effective for some treatments. However, this type of delivery involves tradeoffs because many therapeutic drugs are highly toxic and may cause dangerous side effects when the blood stream carries them to healthy tissue as well as diseased tissue. Thus, a physician must carefully balance the therapeutic benefit of a drug against the toxic side effects that the drug may cause. Additionally, many drugs are expensive and systemic delivery is not an economically efficient method to deliver drugs if the treatment area is limited to a confined region.
Transcutaneous drug delivery systems tend to be localized delivery systems in that the drug is delivered locally to a selected area. However, such drug delivery systems are limited to the application of a drug through the patient's skin or other surface tissue. Thus, the above described drug delivery systems are generally not appropriate for the localized treatment of internal body tissue.
Local drug delivery to a selected internal treatment area would facilitate and/or improve many treatments if the delivery is controlled and the drug is prevented from appreciably affecting tissue outside the treatment area. Such local delivery would allow the delivery of high dosages and concentrations of toxic drugs while reducing the risk of serious side effects. Local internal delivery is also economically efficient because the blood stream does not needlessly transport the drug to healthy tissue.
Percutaneous transluminal coronary angioplasty (PTCA), which dilates a narrowed vessel, is one type of application in which the local delivery of an agent would be advantageous. During PTCA, a catheter is inserted into the cardiovascular system under local anesthesia. An expandable balloon portion is then inflated to compress the atherosclerosis and dilate the lumen of the artery.
Despite the general success of PTCA procedures, the incidence rate of restenosis is 25% and may be as high as 50%. Additionally, as many as 45% of PCTA patients are at risk of acute thrombotic closure. However, the delivery of an appropriate drug during PTCA can limit or prevent restenosis and acute thrombotic closure. The difficulty is that many drugs that are used to prevent these conditions can cause very serious side effects. For example, hirudin and hirulog can cause significant bleeding. Additionally, hirudin can cause impaired renal function (i.e., shut down the patient's kidneys).
Medical researchers have tried various techniques to treat stenosed vessels including the use of lasers, application of heat and the use of intravascular stents. However, many of these are still under investigation with mixed results, while others have generally not been successful. Thus, the ability to administer a drug locally to the dilated portion of the artery in PTCA procedures, without significantly affecting other tissues, would greatly enhance the ability to address the restenosis problem.
The treatment of cancerous tumors or the like is a second example of a medical application in which local drug delivery is beneficial. In the treatment of such tumors, an objective is to administer the cancer drug so that it is localized in the tumor itself. Such drugs are commonly administered systemically through the bloodstream. Various means are then utilized for causing the drug to localize in the cancer tumor. Nevertheless, significant portions of the drugs still circulate through the bloodstream, thereby affecting non-cancerous tissue, producing undesirable side effects, and limiting the dosage of the drug that can be safely administered.
One type of apparatus that has been tried for local drug delivery is a catheter that has a perforated balloon. Early designs typically contemplated the use of a macroporous balloon (i.e., a balloon that has large perforations). This type of design has several shortcomings. For example, a macroporous balloon may realize leakage of inflation fluid during inflation; blood ingress into the balloon during deflation; and have an inability to develop sufficient vacuum in the balloon to either deflate quickly, or to fully deflate thereby providing a low profile for removal; and an inability to decouple balloon inflation from drug delivery.
Minimizing the number of perforations is one solution that has been tried to overcome these shortcomings. However, reducing the number of perforations does not fully address these problems (e.g. blood ingress) and may cause additional shortcomings. For instance, having only a few perforations may result in non-uniform distribution of the drug. Blockages of a few perforations will significantly reduce the amount of drug that can be administered and also makes drug distribution even less uniform.
Additionally, a minimal number of perforations provides only a few paths for the electric current during iontophoresis. The current that flows through the perforations may have a high density and damage the adjacent tissue.
Another problem that results from having a limited number of pores is jetting. The high pressure used during inflation will force the fluid through the perforations at a high velocity, which damages the adjacent tissue. Examples of the damage that can result from jetting include direct tissue damage, formation of edema, and rupturing of the vessel. Additionally, vascular damage due to jetting can lead to the development of intimal hyperplasia, which ultimately results in restenosis.
Accordingly, there is a need in the art for an apparatus that is capable of locally delivering an agent without causing serious tissue damage and that can quickly and completely deflate, thereby increasing maneuverability. There is also a need for such an apparatus that minimizes systemic delivery of the agent and thus reduces side effects. Such an apparatus would be useful for the localized treatment of internal body tissue to limit restenosis following PTCA, to treat cancerous tumors or the like, or to treat other types of maladies.